Wang HL, Zhang SD, Liu T, Liu LM, Pan XY. Innovations in the treatment of endometrial diseases: Role of human umbilical cord mesenchymal stem cells and their exosomes. World J Stem Cells 2026; 18(5): 115486 [DOI: 10.4252/wjsc.v18.i5.115486]
Corresponding Author of This Article
Xiao-Yan Pan, Professor, Center for Reproductive Medicine, Jilin Medical University, No. 5 Jilin Street, Fengman District, Jilin 132013, Jilin Province, China. pxy19790122@163.com
Research Domain of This Article
Obstetrics & Gynecology
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Review
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Wang HL, Zhang SD, Liu T, Liu LM, Pan XY. Innovations in the treatment of endometrial diseases: Role of human umbilical cord mesenchymal stem cells and their exosomes. World J Stem Cells 2026; 18(5): 115486 [DOI: 10.4252/wjsc.v18.i5.115486]
World J Stem Cells. May 26, 2026; 18(5): 115486 Published online May 26, 2026. doi: 10.4252/wjsc.v18.i5.115486
Innovations in the treatment of endometrial diseases: Role of human umbilical cord mesenchymal stem cells and their exosomes
He-Lin Wang, Shi-Dong Zhang, Ting Liu, Li-Mei Liu, Xiao-Yan Pan
He-Lin Wang, Li-Mei Liu, College of Medical Technology, Beihua University, Jilin 132013, Jilin Province, China
He-Lin Wang, Xiao-Yan Pan, Center for Reproductive Medicine, Jilin Medical University, Jilin 132013, Jilin Province, China
Shi-Dong Zhang, Ting Liu, Department of Research and Development, Zhongke Juyan Stem Cell Research Institute, Jilin 132013, Jilin Province, China
Co-corresponding authors: Li-Mei Liu and Xiao-Yan Pan.
Author contributions: Wang HL, Liu LM, and Pan XY conceived and designed the study; Wang HL performed the formal analysis and data curation, and wrote the original draft; Wang HL, Zhang SD, and Liu T conducted the investigation; Wang HL, Zhang SD, and Liu LM provided resources; Wang HL, Zhang SD, Liu T, Liu LM, and Pan XY reviewed and edited the manuscript; Pan XY supervised the project and acquired funding. Liu LM and Pan XY contributed equally to this work as co-corresponding authors. This equal contribution is justified by their distinct and collaborative roles: Liu LM co-conceived the study, provided critical resources, and contributed to manuscript revision; Pan XY co-conceived the study, led the project administration and funding acquisition, and is designated as the corresponding author responsible for all communication with the journal and handling of administrative requirements. All authors have read and approved the final manuscript.
Supported by the Scientific and Technological Research Project of Jilin Province, No. 20240305074YY; and the Industrial Technology Research and Development Project of the Jilin Provincial Development and Reform Commission, No. 2023C027-8.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Xiao-Yan Pan, Professor, Center for Reproductive Medicine, Jilin Medical University, No. 5 Jilin Street, Fengman District, Jilin 132013, Jilin Province, China. pxy19790122@163.com
Received: October 20, 2025 Revised: January 1, 2026 Accepted: February 25, 2026 Published online: May 26, 2026 Processing time: 219 Days and 22.9 Hours
Abstract
Endometrial disorders, notably intrauterine adhesions and thin endometrium, are major causes of female infertility and are often poorly managed by conventional therapies. Human umbilical cord-derived mesenchymal stem cells and their exosomes have emerged as promising regenerative alternatives, leveraging their immunomodulatory, anti-fibrotic, and pro-angiogenic properties. This review provides a critical synthesis of evidence from 125 studies (2007-2025), focusing not only on therapeutic mechanisms and clinical progress but also on the specific hurdles that impede clinical translation. Their mechanistic actions converge on key repair processes, including immune modulation, inhibition of transforming growth factor-β/Smad-mediated fibrosis, and promotion of vascularization. Early phase clinical trials have reported improved endometrial thickness and pregnancy rates, including live births in 30.8%-38.5% of severe intrauterine adhesion cases, with initially favorable safety profiles. The efficacy is further augmented by combining it with biomaterial carriers or estrogen. However, clinical translation is significantly constrained by inherent challenges, including small-scale, heterogeneous trials with short follow-ups; manufacturing complexities due to donor variability and a critical lack of potency assays linking cell phenotype to in vivo efficacy; and unresolved safety concerns, particularly regarding long-term and intergenerational risks, ectopic tissue formation, and context-dependent pro-tumorigenic potential in conditions such as endometriosis and cancer. Therefore, future advancements hinge on addressing these interconnected fronts: Conducting mechanism-informed, large-scale clinical trials, establishing manufacturing standards integrated with biologically relevant potency assays, and resolving context-dependent efficacy and safety paradoxes.
Core Tip: This review offers a critical analysis of human umbilical cord mesenchymal stem cell and exosome therapies for endometrial diseases. It synthesizes compelling mechanistic and clinical evidence while rigorously identifying the key translational roadblocks - standardization, clinical validation, and safety - that must be overcome to move from promising research to widespread clinical practice.
